Ligand-Target Interaction-Based Weighting of Substructures for Virtual Screening

A methodology is introduced to assign energy-based scores to two-dimensional (2D) Structural features based on three-dimensional OD) ligand-target interaction information and utilize interaction-annotated features in virtual screening. Database molecules containing such fragments are assigned cumulative scores that serve as a measure of similarity to active reference compounds. The Interaction Annotated Structural Features (IASF) method is applied to mine live high-throughput screening (FITS) data sets and often identifies more hits than conventional fragment-based similarity searching or ligand-protein docking.